AB0040 STUDYING THE MACROPHAGE ACTIVATION AND THE INTIMA-MEDIA THICKNESS OF THE CAROTID ARTERIES IN UNTREATED PATIENTS WITH RHEUMATOID ARTHRITIS AND SYSTEMIC LUPUS ERYTHEMATOSUS (PRELIMINARY DATA)
Authors: E. Gerasimova, T. Popkova, T. Kirichenko, А. Markin, I. Kirillova, A. Orekhov
Journal: Annals of the Rheumatic Diseases (2022)

Background Autoimmune Rheumatic Diseases (ARDs) occur with a high risk of atherosclerosis development. The macrophages are at the same time a part of the inflammatory response, and also tightly linked to the foam cell formation, thus taking part in both crucial for atherogenesis processes. Objectives To evaluate the macrophage activation, and the intima-media thickness (IMT), subclinical atherosclerosis of the carotid arteries in untreated pts with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Methods Thirty six untreated RA pts (30F/6M) and 36 untreated SLE pts (31F/5M) were enrolled. RA pts had median age of 39 years (range) (33-45), disease duration of 2.5 years (1-5), moderate clinical disease activity DAS of 28 5.3 (3.5;5.8), SDAI of 17 (15;19), HAQ of 1 (0.75;1). SLE pts had median age of 37 years (range) (32-41), disease duration of 3.5 years (1-11), SLEDAI 2K of 7 (4-8), BILAG of 14,5 (10,2-23). Isolation of monocytes was carried out according to the standard procedure for obtaining a leukocyte fraction in a Ficoll gradient and subsequent selection of CD14 + cells using magnetic separation. After isolation, the cells were cultured in X-Vivo medium. To assess the degree of monocyte activation, cells were stimulated by the addition of LPS. The value of monocyte activation was expressed as a ratio of the level of secretion of proinflammatory cytokines by monocytes cultured with and without LPS addition. Secretion levels were determined by ELISA. The belonging of the isolated cells to CD14 + monocytes was additionally confirmed by flow cytometry. All pts undertook carotid duplex ultrasonography. Results Macrophage activation was 8.9 (range) (2.7;40.8) in RA pts and 4.8 (2.3;5.6) in SLE pts (p=0.09). In RA and SLE pts macrophage activation was independent of age, sex, body mass index, cardiovascular risk (CVR) factors (arterial hypertension, overweight, smoking, family history of cardiovascular diseases), activity scores (DAS28, SDAI, SLADAI 2K), and disease-specific autoantibodies levels. In RA pts and SLE pts, the carotid mean IMT (m-IMT) was 0.66 ± 0.12mm and 0.61 ± 0.10mm, the maximum IMT (M-IMT) was 0.76 ± 0.16mm and 0.69 ± 0.14mm, respectively, p&gt;0.05 in both cases. The prevalence of raised lesions (IMT&gt;0.9 mm) were observed in 5 RA pts (14%) and 2 SLE pts (5%); the atherosclerotic plaques (ASP) (IMT ≥ 1.2 mm) – in 7 RA pts (20%) and 6 SLE pts (17%). In RA pts, there was a significant correlation between carotid m-IMT and age (R=0.76), level of total cholesterol (R=0.51), LDL cholesterol (R=0.27), systolic blood pressure (R=0.71), diastolic blood pressure (R=0.78), aMCV levels (R=0.79), p&lt;0,05 in all cases. No correlation between carotid m-IMT/M-IMT and the disease’s duration, stage or activity was found in RA pts. In SLE pts, carotid m-IMT was associated with the mean SLICC/ACR Damage Index score (R=0.50, p=0.01), with antibodies to cardiolipin (aCL) IgG levels (R=0,42, p=0,02), and with antibodies to beta2-glycoprotein 1 (anti-beta2GP1) IgG levels (R=0.49, p=0.01). No correlation between carotid m-IMT/M-IMT and the traditional CVR factors and disease’s activity was found in SLE pts. No association was found between the carotid m-IMT/M-IMT and macrophage activation. Conclusion No differences in macrophage activation were found in RA and SLE pts. Macrophage activation was independent of CVR and ARD-related factors. Subclinical atherosclerotic lesions of the carotid arteries were observed in a every fifth untreated RA and SLE pts. Carotid m-IMT correlated with traditional CVR factors in RA pts, and SLICC/ACR Damage Index score in SLE pts. Our results suggest that there is an association between carotid IMT and immunoinflammatory markers: aMCV in RA pts and antiphospholipid antibodies in SLE pts. A study on a larger number of pts will clarify the link between macrophage activation, autoimmune disorders and carotid atherosclerotic lesions. This work was supported by the Russian Science Foundation (Grant № 22-15-00199). Disclosure of Interests None declared